C6 p.Asp689=
c.2067C>T · rs28651920 · VCV1170475
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 7 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.06%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.2 | GERP -0.014, phastCons 0.99 |
| Overall | ||
| CADD | 12.83 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.06%
African / African-American · 793/74,992 alleles
Filtering AF
0.996%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.972%
Overall
0.06%
968/1,613,664 alleles · low-frequency
exomes 513/1,461,404 · genomes 455/152,260 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.06% | 95 |
| Admixed American | 0.0867% | 1,153 |
| Remaining individualsnot grpmax-eligible | 0.0784% | 1,275 |
| Middle Eastern | 0.066% | 1,514 |
| European (non-Finnish) | 0.00559% | 17,874 |
| South Asian | 0.00329% | 30,361 |
| Finnishnot grpmax-eligible | 0.00156% | 64,022 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- C6
- Protein
- p.Asp689=
- Coding
- c.2067C>T
- MANE Select
- NM_000065
- dbSNP
- rs28651920
- Type
- single nucleotide variant
- Location
- chr5:41155006 (GRCh38)
- Gene constraint
- LOEUF 1.008 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.72 · 11 PDB
- Residue 689
- the sushi 1 domain; the 'c5b-binding domain' region; a β-strand; the 'ccp 2' region
Similar variants
- C6 p.Arg596Ter Pathogenic/Likely pathogenic ★★ same type
- C6 p.Arg606Ter Pathogenic ★★ same type
- C6 p.Cys218Ter Pathogenic/Likely pathogenic ★★ same type
- C6 p.Tyr683Ter Pathogenic/Likely pathogenic ★★ same type
- C6 p.Ala21Val Uncertain significance ★★ ⚠ same type
- C6 p.Ala396Gly Uncertain significance ★★ ⚠ same type
- C6 p.Ala456Thr Uncertain significance ★★ ⚠ same type
- C6 p.Ala500Ser Uncertain significance ★★ ⚠ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/c6-p-asp689 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown